iPLEDGE NON-COMPLIANCE ACTION POLICY

1 Page 1 of 18 iPLEDGE NON-COMPLIANCE ACTION POLICY Effective Date: 7/16/2012 (Version , Updated: 5/15/2017) TABLE OF CONTENTS Page 1. OVERVIEW ..3 2. DEFINITIONS ..3 NON-COMPLIANCE - pharmacy, prescriber, designee or wholesaler..3 Missing Risk Management Authorization--RMA NON-COMPLIANCE ..3 Isotretinoin Products Manufacturing Group (IPMG) ..3 3. PURPOSE OF POLICY ..3 4. NOTIFICATION OF RELATED PARTIES ..3 5. FDA REPORTABLE DEVIATION EVENTS ..4 FDA R eportable Suspension ..4 Temporary Deactivation ..5 Permanent Deactivation ..6 Case Reconsideration ..6 6. INFORMATION REQUIREMENTS ..7 7. INVESTIGATION AND ACTION IMPLEMENTATION ..7 Investigation and ACTION for entities and prescribers not registered in the iPLEDGE Program ..7 NON-COMPLIANCE by designees Impact to prescriber status ..7 NON-COMPLIANCE by delegate Impact to prescriber status.

2 7 NON-COMPLIANCE by pharmacists Impact to pharmacy status ..7 8. CATEGORIES OF ACTION AND CORRESPONDING REMEDIAL MEASURES, INCLUDING DEACTIVATION FOR NON-COMPLIANCE FOR ALL STAKEHOLDERS ..8 9. NON-COMPLIANCE ACTIVITY BY EACH STAKEHOLDER AND CATEGORY ..10 Page 2 of 18 10. INVESTIGATIVE PROCESS FOR DISPENSING WITHOUT AN RMA (REFER TO SECTION ): DID NOT CHECK IN THE iPLEDGE PROGRAM SYSTEM, DISPENSED MEDICATION WITHOUT OBTAINING AN RMA ..16 Methodology ..16 Investigative Process ..17 11. MONITORING AND INVESTIGATION FOR PATIENT MISCLASSIFICATION (REFER TO SECTIONS AND ): INTENTIONAL FALSIFICATION OF PATIENT CLASSIFICATION TYPE DETERMINED TO BE AN ATTEMPT TO VIOLATE PROGRAM Page 3 of 18 1. OVERVIEW The iPLEDGE Risk Evaluation Mitigation Strategy (REMS) Program is a computer based restricted distribution program and pregnancy registry designed to support the public health goals that no woman who is already pregnant will initiate isotretinoin therapy and that no woman will become pregnant while on isotretinoin therapy for one month prior to, during, and for 30 days after the course of treatment.

3 Compliance with the requirements of the iPLEDGE Program is necessary to achieve this public health goal, and potential fetal exposure is paramount when considering actions taken against a non-compliant stakeholder in the iPLEDGE Program. 2. DEFINITIONS NON-COMPLIANCE - For the purposes of the iPLEDGE Program, the definition of NON-COMPLIANCE is a stakeholder (patient, pharmacy, prescriber, designee or wholesaler) that does not meet the requirements of the iPLEDGE Program. Actions qualifying as a NON-COMPLIANCE are specific to the category of stakeholder ( , patient, pharmacy, prescriber, designee or wholesaler). Missing Risk Management Authorization--RMA NON-COMPLIANCE Suspected NON-COMPLIANCE --This means that the iPLEDGE Program sponsors have received information via the iPLEDGE Program system or otherwise indicating that pharmacy X may have dispensed a prescription for patient Y in the past month even though the iPLEDGE Program system indicates that no RMA exists for that patient in the past month.

4 Therefore, pharmacy X is suspected of NON-COMPLIANCE . Confirmed NON-COMPLIANCE --pharmacy X is investigated, and has been found to have dispensed isotretinoin without an RMA. Once confirmed, a pharmacy would incur a Warning-level deviation per the iPLEDGE Program NON-COMPLIANCE ACTION POLICY . Isotretinoin Products Manufacturing Group ( IPMG ) 3. PURPOSE OF POLICY As referenced in the FDA Approval Letter of October 22, 2010, one of the components of the isotretinoin REMS Program is implementation of a plan to monitor compliance, address deviations, and institute appropriate corrective actions to improve minimization of drug exposure during pregnancy and compliance with elements to assure safe use under the iPLEDGE Program . This iPLEDGE Program NON-COMPLIANCE ACTION POLICY sets forth the principles by which NON-COMPLIANCE by iPLEDGE Program stakeholders will be evaluated.

5 4. NOTIFICATION OF RELATED PARTIES The iPLEDGE Program stakeholders involved in reported NON-COMPLIANCE will be contacted as part of the related investigation. Decisions and outcomes of investigations will be communicated to stakeholders via notification letters. The following section Page 4 of 18 identifies the confirmed acts of NON-COMPLIANCE with the iPLEDGE Program requirements that will result in a deviation report being sent to the FDA. 5. FDA REPORTABLE DEVIATION EVENTS The following acts of NON-COMPLIANCE with the iPLEDGE Program requirements, if confirmed through the iPLEDGE Program investigative procedures, will result in a deviation report being provided to the FDA: FDA Reportable Events Distribution or sale of any isotretinoin product to an unregistered and/or un-activated pharmacy or unregistered wholesaler Sale/dispensing of any isotretinoin product by a pharmacy not registered and activated in the iPLEDGE Program Transfer of any isotretinoin product in any manner (sale/borrow/loan) between pharmacies Permanent Deactivations of stakeholders, according to the criteria contained in this POLICY (see Section ) Any other confirmed NON-COMPLIANCE event that the IPMG reasonably believes should be reported to the FDA pursuant to relevant laws and/or regulatory guidance Suspension A Suspension is a temporary, 30-day inactivation of a stakeholder from the iPLEDGE Program, pending implementation of a Corrective ACTION Plan by the stakeholder.

6 A Corrective ACTION Plan for a stakeholder in Suspension must include the following: A root cause analysis for each NON-COMPLIANCE event(s) Remediation plan to prevent recurrence of each type of NON-COMPLIANCE Implementation date for the remediation plan If a Corrective ACTION Plan is not received from a pharmacy within 30 days of the effective date of the Suspension, on day 31 the pharmacy will move to Temporary Deactivation status. If an acceptable Corrective ACTION Plan is not received from the pharmacy within 180 days from the effective date of the Suspension, that pharmacy will be permanently deactivated. For a wholesaler in Suspension, if an acceptable Corrective ACTION Plan is not received within 90 days from the initial Warning-level deviation, that wholesaler will be permanently deactivated. The Suspension is removed and full privileges are restored upon successful implementation of the Corrective ACTION Plan, which is confirmed Page 5 of 18 by the iPLEDGE Program sponsors after monitoring the corrective ACTION process for the first 30 days after reinstatement.

7 A suspended pharmacy or wholesaler will be permitted to retain in-house any isotretinoin inventory acquired prior to the effective date of the Suspension. A suspended pharmacy or wholesaler may not purchase additional isotretinoin until the Suspension is removed. A suspended pharmacy may not dispense isotretinoin from its existing inventory. A suspended wholesaler may not sell and/or distribute isotretinoin to a pharmacy from its existing inventory. If a pharmacy or wholesaler in suspended status is part of a larger entity ( , c hain pharmacy or multi-site wholesaler) the parent entity will be notified of the NON-COMPLIANCE activity and the effective date and expiration date of this status. Temporary Deactivation A Temporary Deactivation is a 90-day deactivation of a pharmacy from the iPLEDGE Program. A Corrective ACTION Plan for a pharmacy that is temporarily deactivated must occur within the 90-day Deactivation period and must include the following: A root cause analysis for each NON-COMPLIANCE event(s) Remediation plan to prevent recurrence of each type of NON-COMPLIANCE Date of resumed operations under the acceptable Corrective ACTION Plan (must be at least 90 days from the effective date of Temporary Deactivation) Documentation that any isotretinoin product in inventory was returned to the appropriate wholesaler/manufacturer or an affidavit that there was no isotretinoin product in inventory at the time of Temporary Deactivation to be returned.

8 If a Corrective ACTION Plan is not received within 90 days of the effective date of the Temporary Deactivation, on day 91 the pharmacy will be permanently deactivated. If an acceptable Corrective ACTION Plan is not received within 180 days from the effective date of the Temporary Deactivation, the pharmacy will be permanently deactivated. The Temporary Deactivation is removed and full privileges are restored upon acceptance of the Corrective ACTION Plan. Once operations are resumed, the iPLEDGE Program sponsors will monitor the corrective ACTION process for the first 30 days. Page 6 of 18 A pharmacy in a status of Temporary Deactivation will be required to return any isotretinoin inventory already acquired prior to the Temporary Deactivation, and may not purchase or acquire additional isotretinoin until the Temporary Deactivation is removed, and may not dispense, sell and/or distribute isotretinoin from such existing inventory during the Temporary Deactivation.

9 If the pharmacy in a status of Temporary Deactivation is part of a larger entity ( Chain pharmacy) the parent entity will be notified of non-compliant activity and effective date and expiration date of this status. Permanent Deactivation A Permanent Deactivation is the stakeholder s permanent removal from participation in the iPLEDGE Program Permanently deactivated prescribers and designees will no longer be able to interact with the iPLEDGE Program for any existing or future patients, effectively removing the capability to provide isotretinoin as a therapy option for the prescriber s patient population. The prescriber s active iPLEDGE Program patient population will be contacted to inform them of the prescriber s Permanent Deactivation. Each active patient will be provided with instructions for transferring to another prescriber if desired. Permanently deactivated prescribers and designees will be added to the program Watch List.

10 Stakeholders on this list are monitored for any further iPLEDGE Program activity including patients in a permanently deactivated prescriber s population who attempt to fill prescriptions without transferring to a new prescriber and any attempt to re-register in the iPLEDGE Program under a different iPLEDGE Program prescriber ID. Permanently deactivated pharmacies and wholesalers will be required to return all existing isotretinoin inventory as per the manufacturer s instructions. If the permanently deactivated pharmacy or wholesaler is part of a larger entity ( , Chain pharmacy or multi-site wholesaler), the parent entity will be notified of NON-COMPLIANCE activity and the effective date of the Permanent Deactivation. Case Reconsideration A stakeholder may request that the result of any investigation into NON-COMPLIANCE activity be reconsidered.